Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study

BackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging ha...

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Main Authors: Michele Bailo, Nicolò Pecco, Marcella Callea, Paola Scifo, Filippo Gagliardi, Luca Presotto, Valentino Bettinardi, Federico Fallanca, Paola Mapelli, Luigi Gianolli, Claudio Doglioni, Nicoletta Anzalone, Maria Picchio, Pietro Mortini, Andrea Falini, Antonella Castellano
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2022.885291/full
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author Michele Bailo
Michele Bailo
Nicolò Pecco
Marcella Callea
Paola Scifo
Filippo Gagliardi
Luca Presotto
Valentino Bettinardi
Federico Fallanca
Paola Mapelli
Paola Mapelli
Luigi Gianolli
Claudio Doglioni
Nicoletta Anzalone
Nicoletta Anzalone
Maria Picchio
Maria Picchio
Pietro Mortini
Pietro Mortini
Andrea Falini
Andrea Falini
Antonella Castellano
Antonella Castellano
author_facet Michele Bailo
Michele Bailo
Nicolò Pecco
Marcella Callea
Paola Scifo
Filippo Gagliardi
Luca Presotto
Valentino Bettinardi
Federico Fallanca
Paola Mapelli
Paola Mapelli
Luigi Gianolli
Claudio Doglioni
Nicoletta Anzalone
Nicoletta Anzalone
Maria Picchio
Maria Picchio
Pietro Mortini
Pietro Mortini
Andrea Falini
Andrea Falini
Antonella Castellano
Antonella Castellano
author_sort Michele Bailo
collection DOAJ
description BackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.ObjectivesThis study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.Materials and MethodsSeventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed.ResultsA highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.ConclusionPreliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.
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spelling doaj.art-42d4eff90ca244f081bb1c2c8c2a75822022-12-22T03:39:07ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-07-011610.3389/fnins.2022.885291885291Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary StudyMichele Bailo0Michele Bailo1Nicolò Pecco2Marcella Callea3Paola Scifo4Filippo Gagliardi5Luca Presotto6Valentino Bettinardi7Federico Fallanca8Paola Mapelli9Paola Mapelli10Luigi Gianolli11Claudio Doglioni12Nicoletta Anzalone13Nicoletta Anzalone14Maria Picchio15Maria Picchio16Pietro Mortini17Pietro Mortini18Andrea Falini19Andrea Falini20Antonella Castellano21Antonella Castellano22Vita-Salute San Raffaele University, Milan, ItalyDepartment of Neurosurgery and Gamma Knife Radiosurgery, IRCCS Ospedale San Raffaele, Milan, ItalyNeuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan, ItalyPathology Unit, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Neurosurgery and Gamma Knife Radiosurgery, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyPathology Unit, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyNeuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDepartment of Nuclear Medicine, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyDepartment of Neurosurgery and Gamma Knife Radiosurgery, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyNeuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan, ItalyVita-Salute San Raffaele University, Milan, ItalyNeuroradiology Unit and CERMAC, IRCCS Ospedale San Raffaele, Milan, ItalyBackgroundTumor heterogeneity poses major clinical challenges in high-grade gliomas (HGGs). Quantitative radiomic analysis with spatial tumor habitat clustering represents an innovative, non-invasive approach to represent and quantify tumor microenvironment heterogeneity. To date, habitat imaging has been applied mainly on conventional magnetic resonance imaging (MRI), although virtually extendible to any imaging modality, including advanced MRI techniques such as perfusion and diffusion MRI as well as positron emission tomography (PET) imaging.ObjectivesThis study aims to evaluate an innovative PET and MRI approach for assessing hypoxia, perfusion, and tissue diffusion in HGGs and derive a combined map for clustering of intra-tumor heterogeneity.Materials and MethodsSeventeen patients harboring HGGs underwent a pre-operative acquisition of MR perfusion (PWI), Diffusion (dMRI) and 18F-labeled fluoroazomycinarabinoside (18F-FAZA) PET imaging to evaluate tumor vascularization, cellularity, and hypoxia, respectively. Tumor volumes were segmented on fluid-attenuated inversion recovery (FLAIR) and T1 post-contrast images, and voxel-wise clustering of each quantitative imaging map identified eight combined PET and physiologic MRI habitats. Habitats’ spatial distribution, quantitative features and histopathological characteristics were analyzed.ResultsA highly reproducible distribution pattern of the clusters was observed among different cases, particularly with respect to morphological landmarks as the necrotic core, contrast-enhancing vital tumor, and peritumoral infiltration and edema, providing valuable supplementary information to conventional imaging. A preliminary analysis, performed on stereotactic bioptic samples where exact intracranial coordinates were available, identified a reliable correlation between the expected microenvironment of the different spatial habitats and the actual histopathological features. A trend toward a higher representation of the most aggressive clusters in WHO (World Health Organization) grade IV compared to WHO III was observed.ConclusionPreliminary findings demonstrated high reproducibility of the PET and MRI hypoxia, perfusion, and tissue diffusion spatial habitat maps and correlation with disease-specific histopathological features.https://www.frontiersin.org/articles/10.3389/fnins.2022.885291/fullhigh-grade gliomaPETMRIhabitatshypoxia imagingperfusion-weighted imaging
spellingShingle Michele Bailo
Michele Bailo
Nicolò Pecco
Marcella Callea
Paola Scifo
Filippo Gagliardi
Luca Presotto
Valentino Bettinardi
Federico Fallanca
Paola Mapelli
Paola Mapelli
Luigi Gianolli
Claudio Doglioni
Nicoletta Anzalone
Nicoletta Anzalone
Maria Picchio
Maria Picchio
Pietro Mortini
Pietro Mortini
Andrea Falini
Andrea Falini
Antonella Castellano
Antonella Castellano
Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
Frontiers in Neuroscience
high-grade glioma
PET
MRI
habitats
hypoxia imaging
perfusion-weighted imaging
title Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
title_full Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
title_fullStr Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
title_full_unstemmed Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
title_short Decoding the Heterogeneity of Malignant Gliomas by PET and MRI for Spatial Habitat Analysis of Hypoxia, Perfusion, and Diffusion Imaging: A Preliminary Study
title_sort decoding the heterogeneity of malignant gliomas by pet and mri for spatial habitat analysis of hypoxia perfusion and diffusion imaging a preliminary study
topic high-grade glioma
PET
MRI
habitats
hypoxia imaging
perfusion-weighted imaging
url https://www.frontiersin.org/articles/10.3389/fnins.2022.885291/full
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